2000 Fiscal Year Final Research Report Summary
Structural analysis of BMP and BMP receptor
| Project/Area Number |
11470475
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Physical pharmacy
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| Research Institution | Osaka University |
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Principal Investigator |
KOBAYASHI Yuji Graduate school of pharmaceutical sciences, Osaka University Professor, 薬学研究科, 教授 (20127228)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIDA Takuya Graduate school of pharmaceutical sciences, Osaka University Research associate, 薬学研究科, 助手 (00294116)
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| Project Period (FY) |
1999 – 2000
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| Keywords | BMP / receptor / structure / NMR / NMR |
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| Research Abstract |
Bone morphogenetic proteins (BMPs) regulate the growth, differentiation and apoptosis of various cells. To elucidate the mechanisms of signal transduction by BMP, we analyzed the structure and interactions of BMP receptor. The extracellular domain of the mouse BMP type-IA receptor was expressed as a fusion protein with thioredoxin in Escherechia coil. Using heteronuclear multidimensional NMR methods, the assignments of the BMP receptor were completed and the solution structure of BMP receptor was determined. In other words, we have obtained powerful tools and methods to investigate the BMP-BMP receptor complex at atomic resolution. Based upon the resulting structure, we have designed and synthesized several mutants of BMP receptor to identify its ligand (i.e. BMP) binding site. CD spectra of the mutant receptors indicated that all the mutants have essentially the native folding structures. Affinities of the mutants to BMP-4 were measured using several physico-chemical methods, surface plasmon resonance sensor (BIACORE), sedimentation equilibrium and NMR.Binding studies have shown that the side chains of Ile52, Glu54, Thr62 and Thr64 at the surface of the three-stranded β-sheet form a high affinity ligand-binding surface together with Phe75 in loop region. These results provide deeper insights for the structural basis of the ligand recognition by BMP receptor.
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[Publications] K.Kato, C.Sautes-Fridman, W.Yamada, K.Kobayashi, S.Uchiyama, H.Kim, J.Enokizono, A.Galinha, Y.Kobayashi, W.H.Fridman, Y.Arata, and I.Shimada: "Structural Basis of the Interaction Between IgG and Fcγ Receptors"Journal of Molecular Biology. Vol.295. 213-224 (2000)
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「研究成果報告書概要(欧文)」より
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[Publications] T.J.Dennis, T.Kai, K.Asato, T.Tomiyama, H.Shinohara, T.Yoshida, Y.Kobayashi, H.Ishiwatari, Y.Miyake, K.Kikuchi, and Y.Achiba: "Isolation and Characterization by ^<13>C NMR Spectroscopy of [84] Fullerene Minor Isomers"Journal of Physical Chermistry A. Vol.103. 8747-8752 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] H.Kashimori, T.Yoshida, H.Kijima, H.Shimahara, S.Uchiyama, T.Ishino, H.Nakano, Y.Shibata, Y.Saihara, T.Ohkubo, T.Yoshida, A.Kaji and Y.Kobayashi: "Backbone NMR assignment and secondary structure of Ribosome Recycling Factor (RRF) from Pseudomonas Aeruginosa"Journal of Biomolecular NMR. Vol.15. 341-342 (1999)
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「研究成果報告書概要(欧文)」より
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